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The ataxia telangiectasia mutated (ATM) gene is critical for the detection and repair of double stranded breaks. Mutations in this gene cause the autosomal recessive syndrome ataxia telangiectasia (AT), a feature of which is a high risk of cancer, particularly lymphoma. We have undertaken a population-based case/control study to assess the role of genetic variation in ATM on the risk of non-Hodgkin lymphoma (NHL) in the general population. The term NHL encompasses several subtypes, many of which have in common the occurrence of specific somatic translocations that contribute to lymphomagenesis. We hypothesize that variants that result in slightly decreased function of ATM could reduce DNA double-stranded break repair capacity, contributing to the occurrence of translocations and subsequent lymphomas. The study population consists of 798 NHL cases and 793 controls that are frequency matched by region, age, sex and ethnicity. Genetic variation in the promoter and all exons of ATM was determined by hi-directional sequencing of the germline (blood) DNA of 86 NHL patients, both T and B-cell. Sequencing revealed 79 variants, 18 of which correspond to amino acid differences. Six of these variants are predicted to be deleterious to protein function; these variants were all rare (0.5-1.1%). Seven of the 86 (8.1%) NHL patients were heterozygous at these loci. Eleven variants were present at a frequency of 5% or greater; these make up 10 haplotypes. Seven tagSNPs were predicted to specify these 10 haplotypes. Linkage disequilibrium across the ATM gene is high but not complete. Six tagSNPs (1 failed in assay design) and the 6 putatively deleterious variants were genotyped in the entire case/control set. Direct association tests based on the tagSNPs and haplotype-based indirect association tests were performed. The six rare variants were also assessed. The results of the association tests indicate that common variants of ATM do not significantly contribute to the overall risk of NHL in the general population. Our results, however, point to the possibility of a rare variant-rare disease model where some rare, functionally deleterious variants may contribute to an increased risk of development of rare subtypes of the disease.